1. Field of the Invention
This invention relates to novel 2-substituted alkyl-3-carboxycarbapenem antibacterials obtained from condensation of a 2-oxocarbapenam-3-carboxylic ester with a stabilized ylide followed by removal of the ester protecting group.
2. Brief Discussion of Disclosures in the Art
2-Substituted alkyl carbapenems are known in the art as exhibiting interesting antibacterial activity. For example, see U.S. Pat. Nos. 4,539,208 and 4,194,047, both assigned to Merck & Co. Inc.
The process generally used for producing these compounds is multistep one whose crucial ring-forming reaction generally involves an internal Wittig reaction as illustrated by the following synthetic scheme: ##STR1##
However the overall synthesis is a lengthy one, and does not work efficiently for certain W groups, e.g., COR, CO.sub.2 R and CN.
Sandoz has recently reported in Tetrahedron Letters. Vol. 25, No. 52, pp. 5989-5992 (1984) the Wittig reaction between 6-fluoroalkyl 2-oxocarbapenam-3-carboxylic esters ketoesters and triphenylphosphorane ylides. However, it is disclosed that difficulties were found in attempting to remove the 3-(para-nitrobenzyl carboxylate) protecting group and that carbapenams and inseparable mixtures were obtained. It is further stated that none of the obtained compounds exhibited interesting antibacterial activity.
3. Objects of the Invention
It is an object of the present invention to provide an improved process for synthesizing 2-substituted alkyl-3-carboxycarbapenems in a rapid and convenient route starting with a readily available 2-oxocarbapenam-3-carboxylic ester. It is further an object to provide a process yielding novel 2-substituted alkyl-3-carboxycarbapenems separated from their relatively inactive 2-substituted alkylidene-3-carboxycarbapenam by-products. These and other objects of the invention will be obvious to one skilled in the art from the following disclosure.